Novel intra-ocular lens for extended macular vision in patients with macular degeneration

ABSTRACT

An intraocular lens system comprising a single lens comprising two optical surfaces selected to maintain image quality at the foveal centre whilst reducing image aberration at preferred retinal locus locations outside of the fovea region.

CROSS-REFERENCE TO RELATED APPLICATIONS

This non-provisional US utility patent application claims the benefit ofpriority from U.S. provisional patent application No. 62/770,999, filed23 Nov. 2018. The disclosure of such provisional application is herebyincorporated by reference in its entirety where appropriate forteachings of additional or alternative details, features, and/ortechnical background, and priority is asserted from each.

BACKGROUND

In the decades since intraocular lenses (IOLs) were first introduced,the primary focus has been on optimising visual outcomes innormally-sighted individuals undergoing clear lens extraction andcataract surgery. This has led to the development of injectable softacrylic IOLs, designed to minimise surgically-induced astigmatism, andaspherical lens optics to counter the age-related positive sphericalaberration of the cornea. Standard soft acrylic intraocular lenses arenow capable of delivering a tightly focused image at the fovea andconsistent, high quality visual outcomes, in patients with otherwisehealthy eyes. However, the quality of the image supplied by such lensesdrops off significantly only a few degrees outside of the centre of thefovea and this may have significant implications for visual outcomes inpatients with macular disease who often adopt eccentric fixation to makeuse of healthier retina outside of the foveal centre. Eyes withage-related macular degeneration have poor contrast sensitivity andscotomata (often centre-involving) that make them particularly sensitiveto reductions in retinal image quality. Patients with center-involvingmacular disease can expect to have a degraded quality of vision withstandard intraocular lenses that compounds the poor contrast sensitivityand patchy photoreceptor loss associated with conditions such asage-related macular degeneration (AMD). Furthermore, as conditions suchas AMD progress, patients can expect the quality of the images suppliedto preferred retinal loci to worsen as more of the macula becomesaffected.

Surgical options for patients with macular pathology undergoing cataractextraction and intraocular lens implantation are extremely limited. Todate, surgeons have largely used standard monofocal IOLs to targetemmetropia and tightly focus the image at the foveal centre in such.patients; however, the quality of the image supplied by standard IOLsdrops off rapidly at only 4 degrees of retinal eccentricity(approximately 1.15 mm), despite cone density still being relativelyhigh, at approximately 20000/mm², in this area¹³.

Alternatives include the implantation of intraocular telescopes toprovide a magnified image or the use of prismatic devices to target asingle PRL. Some devices employ a combined approach. Patients with AMDfrequently depend on the use of multiple preferred retinal loci tocomplete activities of daily living, so targeting a specific PRL has thedisadvantage of compromising image quality at other retinal loci usedfor activities of daily living. Any image optimisation at a specific PRLmay also become completely redundant if a patient starts to rely onanother PRL as the disease progresses.

Intraocular telescopes attempt to build on the advantages of hand-heldmagnifiers by conferring the optical advantages of intraocularmagnification and eliminating the need for hand-eye coordination. Suchdevices are often relatively large and complex when compared withstandard IOLs and are more difficult to implant safely. A key drawbackof intraocular telescopes, depending on the degree of magnification, isthe reduction in peripheral visual field that results. With somedevices, the peripheral field may be so constricted that implantation isonly possible in one eye. Intraocular telescopes also disperse thefinite amount of light across a wider area of retina, so inevitablyreduce the contrast of the resulting image. Both intraocular telescopesand prismatic devices may therefore compromise patients' naturalmechanisms for coping with central field loss and therefore impact onvisual function because both contrast sensitivity and fixation stabilitycorrelate with reading ability. Similarly, reading function is likely tohe disrupted if a device is only implanted in one eye by compromisingbinocular summation and affecting the scanning of the image across themacula that occurs during reading.

The evolution herein of a single, injectable, soft polymeric (e.g.,acrylic) intraocular lens for implantation in the capsular bag, withoptics uniquely configured to supply a focused image to all areas of themacula extending up to 10 degrees from the foveal centre is an advanceon existing technologies. The optic is designed to maintain imagequality at the centre of the fovea for patients with early disease. Bycorrecting for optical aberrations generated when patients fixateeccentrically out to up to 10 degrees of retinal eccentricity, theembodiment IOL optimises visual potential in macular disease andprotects against progressive visual loss. A target of +2D to +3.5D withsuch a novel intraocular lens may also afford 10-20% magnification withglasses but this is not essential to the mechanism of action.

BRIEF SUMMARY OF INVENTION

In an embodiment of the present invention, there is provided asingle-piece, injectable, soft, hydrophobic polymeric (e.g., acrylic)intraocular lens designed for siting in the capsular bag. The lensoptics are uniquely optimised to provide an enhanced quality of imageanywhere in the macula from 0 degrees up to 10 degrees of eccentricfixation in any direction from the foveal centre. Embodiment lensesachieve their effect through being shaped to minimise the opticalaberrations that would be generated by a standard lens if a patient wereto fixate eccentrically. Embodiment lenses are designed to have radiiand conic constants that provide for a focused image at the fovealcenter and a reduction in high order aberrations over an area extendingup to, but not necessarily restricted to, 10 degrees from the focalcenter in all directions of gaze.

The novel lens delivers superior image quality compared with standardmonofocal IOLs at increasing degrees of retinal eccentricity withpotential benefits for patients with macular pathology. An embodimentIOL may be used to target a hypermetropic post-operative refraction: atarget of +2D to +3.5D may afford 10-20% magnification with glasses.Emmetropia or myopic outcomes may be targeted in individuals with bettervisual potential or to avoid post-operative anisometropia, as with astandard monofocal IOL.

Embodiment IOL powers are available in dioptric powers of 11, 13, 15,17, 19, 21, 23 and 25 D, but an embodiment IOL is not restricted to thisrange of dioptric powers. Suitable IOL power for an individual eye maybe estimated using the SRK/T (or similar) biometric formula and anA-constant of 119.2, in a similar manner to standard IOLs implanted atthe time of cataract surgery.

An embodiment IOL offers clear advantages over existing intraoculartelescopes in the management of macular disease. By comparison,intraocular telescopes such as the Implantable Miniature Telescope (IMT)and the Intraocular Lens for Visually Impaired People (IOL-Vip™) arecostly and complex devices, comparatively, that have risk-benefitprofiles rendered less attractive by the need for large incisions in theeye, reductions in visual field, the risks of corneal decompensation andthe need for post-operative visual rehabilitation^(11,12)

In an embodiment, the invention is a single-piece, injectable, soft,hydrophobic polymeric (e.g., acrylic) IOL designed for sitting in thecapsular bag. The lens optics are uniquely optimized to provide anenhanced quality of image across all areas of the macula extending 10°from the foveal center and the device therefore constitutes a new classof IOL.

As set forth in Example 1, the lens delivers superior image qualitycompared with standard monofocal IOLs at increasing degrees of retinaleccentricity with potential benefits for patients with macularpathology. The inventive IOL embodiment may also be used to target ahypermetropic postoperative refraction. For example, a target of +2.00to +3.50 diopters affords 10% to 20% magnification with glasses, but thedegree of hypermetropia may be increased or reduced depending on theseverity of the maculopathy and the patient's preference or suitabilityfor this approach. Emmetropia or myopic outcomes may he targeted inindividuals with better visual potential or to avoid postoperativeanisometropia, as with a standard monofocal IOL.

In embodiments there is provided an intraocular lens system forimproving patient's vision enhancing the quality of image across allareas of the macular extending 10% from the foveal center comprising alens having a first surface and a second surface, and providing anoptical power of P diopters; the lens being characterized by an opticalzone diameter(D) and a central thickness(T); the first surface isspherical having a first radius of curvature (R₁); the second surface isa rotationally symmetric conic surface, having a second radius ofcurvature (R₂), and having surface sag (z coordinate) which is afunction of a radial coordinate (r) is given by:

${{{z = \frac{cr^{2}}{1 + \sqrt{1 - {( {1 + k} )c^{2}r^{2}}}}}\mspace{14mu}{where}\text{:}\mspace{11mu} c} = {1/R_{2}}}\;$k = constant

In a specific embodiment, the preferred variables are P=11 diopters,D=6.00 mm, T=0.7 mm, R₁=19.99 mm, R₂=−143.7 mm, and k=−12.7. In anotherspecific embodiment, the preferred variables are P=17 diopters, D=6.00mm, T=0.7 mm, R₁=110.53 mm, R₂=−12.96 mm, and k=−12.7. In an additionalspecific embodiment, the preferred variables arc P=25 diopters, D=6.00mm, T=0.7 mm, R₁=−45.52 mm, R₂ is in the range from −6 mm to −19 mm, andk=−12.7.

DESCRIPTION OF DRAWINGS

Embodiments of the invention are illustrated in the accompanyingdrawings in which:

FIG. 1 is a schematic diagram of the design process.

FIG. 2 is a profile view of an embodiment IOL, providing 17 diopteroptical power.

FIG. 3 is a profile view of an embodiment IOL providing 19 diopteroptical power.

FIG. 4 is a profile view of an embodiment IOL providing 21 diopteroptical power.

FIG. 5 is a profile view of an embodiment IOL, providing 23 diopteroptical power.

FIG. 6 is a profile view of an embodiment IOL providing 25 diopteroptical power.

DETAILED DESCRIPTION

Standard monofocal IOLs provide a focused image to the fovea. Inpatients with dry AMD, central GA often results in a loss of functionalvision at the fovea. However, there is still sufficient receptordensity/visual function in the peripheral macula, to enable patients tomaintain functional vision if the patient is able to fixateeccentrically.

The invention, as herein disclosed in embodiment IOLs, is designed tomaintain image quality at the foveal centre but correct the opticalaberrations that would be generated by a standard monofocal IOL when theeye is tilted to adopt eccentric fixation. This optimises image qualityin any area within 10 degrees of the foveal centre thereby facilitatinguse of these areas as PRLs and resulting in improved functional outcomesafter implantation. The objective is to provide good retinal images atup to 10 degrees of eccentricity with the option of mild magnificationwhen combined with an external spectacle to correct for a maximum +3Drefractive target.

The embodiment IOL design may be carried out using commerciallyavailable ray-tracing software (Zemax OpticStudio, Zemax LLC, USA) in aneye model describing an average eye taken from the literature(Liou-Brenan: Liou H L, Brennan N A. Anatomically accurate, finite modeleye for optical modelling. J Opt Soc Am A. 1997;14(8)1684-1695.). FIG. 1is a schematic diagram of an embodiment of the design process

Ray-tracing techniques may he used to optimize the optical performanceof different IOLs within the previously described eye model. An opticaldesign software may be employed (Zemax OptieStudio, Zemax LLC, USA).Once the materials are selected, a merit function may be developed todesign the embodiment IOLs. In general, the parameters may be selectedacross those of relevance for the intended performance of the lens.During the optimization procedure, different values may besystematically given to the independent variables. Subsequently, thosemay be employed to calculate the selected merit function components. Thetarget is to find a set of values for the variables that minimize themerit function. In the ideal case, the procedure finishes with thefinding of a global or absolute minimum, rather of a local minimum. Themerit function generated incorporated constraints for the geometricalparameters of the IOL to keep them within physiologically compatibleranges. The variable parameters for the optimization, in this example,were the thickness of the lens, its position within the capsule, theradius of curvature, and the asphericity of the different surfaces.Three configurations were simultaneously included in the merit functioncorresponding to incoming beams on axis, at 5, and at 10 degrees ofeccentricity in the horizontal direction.

Embodiment IOLs have the following features in common:

-   -   The front surface is a standard spherical surface with range or        radius of curvature.    -   The rear surface is a rotationally symmetric conic surface. The        surface sag (z coordinate) as a function of the radial        coordinate r is given by:

$z = \frac{cr^{2}}{1 + \sqrt{1 - {( {1 + k} )c^{2}r^{2}}}}$

-   -   where c is the inverse of the radius of curvature R: c=1/R

For a specific non-limiting 17D version of the lens, the relevantparameters are:

-   -   Optical zone diameter: 6.00 mm    -   Central thickness: 0.7 mm    -   1st (front) surface:        -   Standard spherical surface        -   Radius of curvature 110.53 mm    -   2nd (rear) surface:        -   Rotationally symmetric conic surface. The surface sag (z            coordinate) as a function of the radial coordinate r is            given by:

$z = \frac{cr^{2}}{1 + \sqrt{1 - {( {1 + k} )c^{2}r^{2}}}}$

for the anterior and posterior surfaces, respectively), refractive indexof 1.54 and a thickness of 0.70 mm, was used.

To assess the embodiment IOLs' image quality the NIMO instrument(LAMBDA-X, Nivelles, Belgium) is used, which includes an optical bench,together with its software version 4.5,15. The working principle of thisinstrument is based on a phase-shifting schlieren techonology^(71/72).By combining the principle of schlieren imaging with the phase-shiftingmethod, the NIMO instrument allows the measurement of light beamdeviations, which can be used to calculate the wavefront analysisconsidering the 36 Zernikes coefficients. This technology has been shownto effectively measure in vitro optical quality of intraocular lenses.The apparatus complies with the International Standard Organization(ISO) 11979-216. All IOLs were measured while being immersed in a salinesolution whose composition was 0.154 milliequivalents per milliliter ofNaCl (Laboratories Sterop SA, Anderlecht, Belgium). The cuvettes or wetcells used to hold the IOLs and the saline solution in place during themeasurements have been verified by means of an interferometer; and wereshown to have a power <0.005 D. This additional cross-check on the wetcells was carried out to rule out potential interferences with themeasurement. Moreover, accurate power measurements are only possible ifthe setup has been, thoroughly calibrated, which is why the instrumentwas calibrated for each measurement.

In Example 1 detailed below, the axial length of the eye model was setat 23.5 mm. Corneal parameters (curvature, asphericity, thickness andrefractive index) were taken from the Liou-Brennan eye model(reference). The retina was simulated as a −12 mm sphere and theanterior IOL surface was placed axially at 4.16 mm from the secondsurface of the cornea.

The external spectacle lens was modelled using a refractive index of1.585 (polycarbonate) and, a central thickness of 5 mm placed at 12 mmfrom the conical apex (vertex distance). Radii of curvature were 32 mmand 36 mm for the front and back surfaces respectively (1-3 dioptres).Additionally, a +6 D spectacle lens (with the object placed at 33 cmfrom the cornea), with the same front curvature but a posterior radiusof curvature of 44.7 mm, was simulated. All calculations were performedat a wavelength of 550 mm and a pupil diameter of 3 mm.

The embodiment IOL lens was optimized for a Refractive Index of 1.54(for 550 nm) and Abbe Number of 40 and for a thickness of 0.70 mm.

This optimization procedure was repeated for different models withdefined axial length values. This provides optimized lenses fordifferent powers. FIGS. 2 through 6 show the actual shape of theoptimized embodiment IOLs of different powers. The correspondingemmetropic target is at the bottom of each lens. Using these methodologysettings and targets, for this non-limiting example: as the dioptricpower of the IOL increases, the posterior surface of the lens becomesmore curved while the anterior surface changes the sign of thecurvature, running from positive curvature to a flatter curvature andthen negative curvature. This is the consequence of the shape factoroptimization procedure for each model.

EXAMPLE 1 The Study

A study was designed and conducted to assess safety and initial outcomesfollowing implantation of this novel intraocular lens in patients withadvanced, bilateral age-related macular degeneration. Eight eyes of 7subjects with ≤1+ cataract (no LOCSIII grading parameter >2), bilateral,advanced geographic atrophy/dry age-related macular degeneration (AMD)and preoperative corrected distance visual acuity ≥0.60 (CDVA; LogMAR),underwent lens extraction and IOL implantation with a hypermetropicpost-operative refractive target. The amount of targeted post-operativehypermetropia was decided on after careful discussion with the patientregarding the potential benefits of magnification afforded withspectacles using this approach, balanced with the disadvantages ofincreased glasses dependence for activities of daily living. Allpatients had moderate-to-severe visual loss in the operated eye and soopted to have hypermetropic outcomes of 1.5D to 4.5D depending onindividual circumstances (including agreement to proceed with surgery onthe second eye if necessary). Initial follow-ups and assessments wereundertaken at baseline, 1 week, 1 month and 2 months.

The following investigations were performed at baseline and 1 week, 1month and 2 months post-operatively: full subjective refraction,corrected near visual acuity (N-point at 30 cm with LogMAR conversion),corrected distance visual acuity (Log:MAR), intraocular pressure(Goldmann applanation tonometry), specular microscopy (Nidek CEM-530,Nidek Co, Ltd.; 3 acceptable images derived from the central cornea),clinical examination, anterior segment OCT (Visante, Carl Zeiss MeditecAG) and macular OCT (Stratus OCT™ Carl Zeiss Meditec, Germany).Lenticular opacities were graded according to the LOCSIII system. Visualfields were assessed by full-threshold 80-point testing. Reading acuity,critical print size and reading speed were assessed using the MNREADchart after refractive error correction at 1 month post-operatively inthe operated eye. Microperimetry was performed at baseline and at 1-2months post-operatively using the Macular Integrity Assessment (MAIA,Ellex Medical Lasers Ltd.); additional microperimetric assessments wereperformed 1-3 months apart to confirm any changes observed.Microperimetry was undertaken under mesopic conditions with no mydriasisusing the ‘expert’ algorithm to assess macular threshold sensitivity andfixation stability (37 points tested in a 10-degree area centred on thepreferred retinal locus; 4-2 strategy; stimulus size Goldmann III withduration 200 ms). Exclusion criteria included: active choroidalneovascularisation (CNV) treated within 6 months of recruitment; axiallength >24.5 mm or <20.5 mm; uncontrolled glaucoma and intraocularsurgery within 6 months of recruitment.

The mean age of patients was 77+16 years (range 43-91) with amale-female ratio of 5:3. Surgery was performed by a single surgeon(MAQ) using standard techniques. Topical mydriatic agents were used forpupil dilation and anaesthesia was induced by sub-Tenon's delivery. A 5mm capsulotomy and crystalline lens fragmentation were undertaken usinga femtosecond laser surgery platform (LenSx®, Alcon®, Fort Worth, Tex.,USA) and lens extraction completed using the WHITESTAR Signature®phacoemulsification system (Abbot Medical Optics, Abbot LaboratoriesInc., Illinois, USA) with a standard 2.6 mm corneal incision sited at100°. The capsular bag was filled with a cohesive ophthalmicviscoelastic device (OVD) and the lens then loaded into the injectorcartridge, followed by injection into the capsular bag via the mainwound, centration of the lens and OVD/balanced salt solution exchange.All subjects achieved a post-operative spherical equivalent within 1D ofthe targeted refraction (mean ±2.9+1.3D).

Results

Specular microscopy revealed mean of reductions in endothelial cellcounts post-operatively to be 13±14% (range 0-37%). 2 eyes hadreductions of 37% and 31%—this subject was lost to follow-up after 2weeks and lack of drop compliance may account for these changes. Resultswere otherwise in line with reductions expected following standardphacoemulsification cataract surgery (4-13%)⁸. 80-point visual fieldtesting results were similar pre- and post-operatively (mean number ofpoints seen was 50±31 pre-operatively compared with 53±27post-operatively) and anterior segment and macular OCT imaging revealedwell-centred IOLs and stable maculae post-operatively. Intraocularpressures remained stable in all subjects post-operatively—mean pre- andpost-operative intraocular pressures were 16±2.8 mmHg and 14±2mmHg,respectively at 2 months.

Post-operative MN read data were unavailable for one subject. In theremainder we observed modest improvements in mean reading acuity from1.07±0.31 LogMAR to 0.9±0.37 LogMAR and in critical print size from1.04±0.25 to 0.95±0.27. Mean reading speed was observed to increase from28±19 words per minute to 44±31 words per minute, an improvement of 57%.

Microperimetry data were obtained at approximately 1 and/or 2 monthspost-operatively in all but one of the subject eyes. A mean improvementin microperimetry threshold sensitivities from 8.2±4.6 dB to 1.2.0±5.6dB was observed. The mean percentage of fixation points within a4-degree circle increased from 77±17% to 91±11%. Whilst post-operativemicroperimetry data were unavailable for one subject visual acuitiesimproved significantly in this individual post-implantation. Minimalchanges on microperimetric testing were observed in three eyespost-operatively with evidence of incremental improvements at 1 and 2months in the remainder.

Further microperimetry testing for three of the operated eyes wasundertaken and these data indicated incremental improvements in visualfunction beyond the 2-month time-point. Preferred retinal loci in theseeyes were observed to shift progressively away from areas of geographicatrophy. In subject eye 1, the average threshold sensitivity increasedfrom 0 dB to 16.6 dB at 5 months with an associated increase in meanpercentage of fixation points within a 4-degree circle from 64% to 94%.For this subject's second eye, testing at 4 months post-operativelyindicated a slight reduction in average threshold sensitivity from 4.2dB to 3 dB but an increase in the mean percentage of fixation pointswithin a 4-degree circle from 57% to 93%, these points were concentratedin a narrow corridor between the optic disc and a large area ofgeographic atrophy. Testing in a third subject at 4 months showed anincrease in threshold sensitivity from 112.9 dB to 27 dB and a slightdecrease in mean percentage of fixation points within a 4-degree circlefrom 99% to 83%.

No symptoms of aniseikonia were reported but all subjects later went onto have their other eye implanted with the device.

Visual outcomes in study subjects with moderate-to-severe age-relatedmacular degeneration that were consistent with the results of laboratorysimulations, with the equivalent of a mean improvement in distance andnear acuities of 18 ETDRS letters and a 57% increase in mean readingspeed were observed. These results compare very favourably withpublished cataract surgery outcomes in AMD patients, including thoseundergoing treatment for CNV—recent meta-analysis indicated thatsubjects with AMD, undergoing cataract surgery and implantation withstandard monofocal IOLs, can expect improvements in visual acuities of6.5-7.5 ETDRS letters after 6-12 months of follow-up^(9.10).

Statement Regarding Preferred Embodiments

While the invention has been described with respect to the forgoing,those skilled in the art will readily appreciate that various changesand/or modifications can be made to the invention without departing fromthe spirit or scope of the invention as defined by the appended claims.

1. A method for manufacturing an intraocular lens (IOL) system forimproving patient's vision, the method comprising: providing a lenshaving a first surface and a second surface, and an optical power of Pdiopters; said lens being characterized by an optical zone diameter (D)and a central thickness (T); said first surface is spherical having afirst radius of curvature (R1); said second surface is a rotationallysymmetric conic surface, having a second radius of curvature (R2), andhaving surface sag (z coordinate) which is a function of a radialcoordinate (r) is given by:$z = \frac{cr^{2}}{1 + \sqrt{1 - {( {1 + k} )c^{2}r^{2}}}}$where: c=1/[[R]]r, k=conic constant; wherein as the dioptric power ofthe lens increases by more than one diopter, the conic constant remainsconstant.
 2. The method of manufacturing, in accordance with claim 1,wherein as the dioptric power of the lens increases, the posteriorsurface of the lens becomes more curved while the anterior surfacechanges the sign of the curvature, running from positive curvature toflatter and then negative curvature.
 3. An method of manufacturing, inaccordance with claim 1, where: P=11 diopters D=6.00 mm T=0.7 mmR1=19.99 mm R2=−143.7 mm k=−12.7.
 4. The method of manufacturing, inaccordance with claim 1, where: P=17 diopters D=6.00 mm T=0.7 mmR1=110.53 mm R2=−12.96 mm k=−12.7.
 5. The method of manufacturing, inaccordance with claim 1, where: P=25 diopters D=6.00 mm T=0.7 mmR1=−45.52 mm R2-6 to −19 mm k==−12.7.